1. Field of the Invention
This invention relates to the selective separation of strontium-82 from other radioisotopes, such as those resulting from an irradiated molybdenum target, and in the manufacture of a rubidium-82 generator.
2. Background of the Related Art
The use of radioisotopes as diagnostic and imaging agents in medicine has expanded rapidly in recent years. Positron (β+) emitters are particularly useful in the study of metabolic processes because the positron-electron annihilation reaction produces a pair of gamma rays with an energy level of 511 keV travelling in opposite directions. By placing a series of detectors around a patient who has been administered a positron emitter, both the location and amount of radioactivity can be accurately determined. This property is utilized in Positron Emission Tomography (PET) to image metabolic processes in vivo. Rubidium-82 (82Rb) is a short-lived positron-emitting isotope (T1/2=75 seconds) that is increasingly being used to study blood flow through the heart and brain. Physiologically, rubidium is an analogue of potassium, and consequently enters the body's large potassium pool, which has a comparatively slow turnover. Thus, after 82Rb is injected intravenously, the tracer's uptake in tissue reflects the rate of delivery, i.e. blood flow, and thus 82Rb rapidly builds up in the heart. This can be used, for example, to study blood-brain barrier leakage and heart muscle perfusion.
The short half-life of 82Rb means that it must be supplied to physicians in the form of a generator, where the parent 82Sr (T1/2=25 days) is immobilized on a solid substrate or support and 82Rb eluted as required. The generators that are currently available use hydrous tin oxide to immobilize the 82Sr and allow the elution of 82Rb by saline or other appropriate eluant. The 82Sr (T1/2=25 days) is accompanied by unwanted 85Sr (T1/2=64 days), generated as a by-product during the manufacture of 82Sr, wherein both isotopes have a relatively long half-life and a high radiotoxicity due to their tendency to accumulate in bone. Thus, it is essential to minimize or eliminate the introduction of 82Sr and 85Sr into a patient during the administration of 82Rb. Although hydrous tin oxide has proved acceptable to date for use in generators, new materials exhibiting far higher strontium affinities, improved strontium/rubidium separation factors and greater radiolytic stability are needed in order to lower the amount of 82Sr and 85Sr released during elution of the 82Rb.
The parent 82Sr is generated by the proton irradiation of rubidium, rubidium chloride or molybdenum targets followed by dissolution and processing to isolate the 82Sr. The demand for 82Rb generators has grown so great that there is a need to reduce processing times and to increase the yield of 82Sr from processed targets. One method of improving the supply of 82Sr is to improve the processes used to extract 82Sr from irradiated targets. Current methods utilize organic ion exchange or chelating resins to extract very low levels of strontium from dissolved targets containing molar concentrations of inert ions. However, a satisfactory separation of 82Sr from the target materials and other radioisotopes generated during the irradiation procedure requires multiple treatment steps due to the relatively low affinity and low selectivity of the organic ion exchange resins for 82Sr.
82Sr is produced by the proton irradiation of molybdenum metal, rubidium metal and rubidium chloride targets. The irradiation process also produces a range of other radioactive isotopes (e.g. 88Y, 88Zr, 85Sr) and as a consequence, a series of carefully designed separation procedures have been designed to separate the desired 82Sr from other radioisotopes and inactive species present. The primary method used to separate 82Sr is by a series of ion exchange and selective elution steps. Typically, AG 50 W-X8 ion exchange resin is used to separate 82Sr from dissolved targets. However, this resin is relatively non-selective and will absorb numerous polyvalent cations (e.g., 88Y) in addition to the desired 82Sr. Consequently, multiple separation steps are required to isolate 82Sr from the other isotopes present.
82Rb can be conveniently supplied to physicians in the form of a generator in which the parent 82Sr is immobilized on an ion exchange material and the 82Rb eluted when required. This means that 82Rb PET can be performed at clinical facilities where a typical generator may last several months before the yield of 82Rb diminishes below a usable level.
To be suitable for use in a 82Rb generator, an ion exchange material must exhibit a high affinity for strontium but a low affinity for rubidium, allowing the 82Rb daughter to be eluted from a column containing immobilized 82Sr. Generators have been proposed that were based on a number of separation media including CHELEX 100 ion exchange material, Al2O3, Sb(V) hexacyanoferrate, polyantimonic acid, titanium vanadate and hydrated tin(IV) oxide, with the hydrated tin(IV) oxide being the most widely used.
However, the crucial component of any system is the actual ion exchange material containing the immobilized 82Sr parent. Current systems using hydrous tin oxide have a limited life due to the breakdown of the hydrous tin dioxide, necessitating frequent replacement.
Therefore, there is a need for a highly strontium selective ion exchange material in place of ion exchange resins and hydrated tin(IV) oxide, so that the separation and recovery of 82Sr from Rb, RbCl and Mo targets is greatly facilitated. This will lead to a reduction in processing steps, a decrease in target processing times and thus a decrease in the cost of the 82Sr product. There is also a need for an ion exchange material suitable for use as a 82Rb generator having a very high selectivity for 82Sr and a very low selectivity for 82Rb to allow elution of the 82Rb by isotonic saline or other solutions.